1. Field of the Invention
The present invention relates to a method for treating brain injury in a subject. The present invention relates particularly a method of using a neuropeptide to treat brain injury in a subject.
2. Description of Related Art
Spontaneous intracerebral hemorrhage (ICH) accounts for approximately 15% of stroke incidents in Western populations, and may even be higher (up to 20 to 30%) in Asian populations (Qureshi et al., 2001). Being one of the most lethal forms and destructive type of stroke, mortality of ICH is high at 30% to 50% (Rosamond et al., 2008). The prognosis of patients with ICH is poor.
Despite a number of promising trials, no medical or surgical therapy has been convincingly shown to benefit ICH patients (Hanggi and Steiger, 2008). No drug can convincingly benefit patients and effectively increase survival in ICH patients (Pouratian et al., 2003). The early surgical removal of the blood clot has shown no overall benefits when compared with conventional therapies (Hankey and Hon, 1997; Mendelow et al., 2005; Morgenstern et al., 2001).
Pathological changes of ICH can be divided into primary and secondary brain injury. Primary injury occurs rapidly as a result of physical destruction of tissues, and mass effect of the hematoma leading to increased intracranial pressure (Qureshi et al., 2001). Secondary injury commonly occurs when tissue reacts to the invasion of the blood breakdown components in the parenchyma adjacent to hematoma, initiating the activation of inflammatory cells, brain edema, blood-brain bather (BBB) disruption and apoptosis. Secondary injury often takes hours to days after ICH insult (Wang, 2010), making it a practical therapeutic target.
Urocortin, a 40-amino-acid endogenous neuropeptide, belongs to the corticotrophin releasing hormone (CRH) family, sharing two G-protein coupled receptors, CRH-R1 and CRH-R2 (Fekete and Zorilla, 2007; Hsu and Hsueh, 2001). Urocortin is expressed in brain neurons and glial cells (Pedersen et al., 2002; Perrin and Vale, 1999; Stevens et al., 2003; Van Pett et al., 2000), in a variety of brain regions including the supraoptic nucleus, Edinger-Westphal nucleus and the sphenoid nucleus (Pan and Kastin, 2008).
Besides being involved in the regulation of anxiety, learning and memory, body temperature, stress responses (Pan and Kastin, 2008) and hypotension (Fekete and Zorilla, 2007; Torpy et al., 1999), urocortin is also a powerful anti-inflammatory agent and a potential therapeutic drug for heart ischemia/reperfusion injury (Brar et al., 2000; Gordon et al., 2003; Lawrence et al., 2002; and Liu et al., 2005).
As such, in view of the limitations of current management therapies on ICH-induced brain injuries, additional strategies to combat ICH-induced brain injuries need to be provided. The present invention provides such strategies that can effectively reduce the incidence of ICH-induced brain injury.